Definition of aging at the cellular level has met with little success and the presence of great number of existing incomplete hypotheses on the aging process is indicative of the need for rigorous investigation to provide data necessary for bringing order to this area. When dealing with smooth muscle, it is important to determine whether age-related changes are specific for either a single transmitter or a class of agents. Acetylcholine (ACh) is a very important neurotransmitter in the body. The rat, mice and guinea-pig ileum, and the smooth longitudinal muscle of guinea-pig isolated ileum are very widely used pharmacological preparations in pharmacodynamic studies. "Muscarinic Receptor" is a subtype of cholinergic receptors which are specifically stimulated by ACh in these preparations. Accordingly, this proposal is developed for the purpose of using these preparations in vitro to answer two basic questions: 1) Does the sensitivity of the muscarinic receptor change with age? 2) Is the change reflected in the potency of mepenzolate (a specific anti-muscarinic agent) at the receptors? The approach is to measure the ED50 of ACh on preparations from each age group for each species and the pA2 values obtained directly from Schild plots. The ages of the animals from which the tissue will be prepared are: 0.75, 3.0, 6.0, 18 and 24 months for guinea-pigs; and young (1.0 month), mature (3.0 months), old (6.0 months) and very old (24 months) for mice and rats. The data generated in this investigation will not only be useful in helping to interpret some incomplete data in literature and the understanding of the multi-faceted aspects of the aging process at the cellular level, but will also provide the necessary preliminary data for us to develop a major proposal on the "Effects of aging on the components of parasympathetic system" which we are currently developing for submission to NIA (National Institute of Aging) to be considered for funding.